POS0386 IMMUNE CHECKPOINT INHIBITORS: FAIL TO KEEP A CHECK ON AUTOIMMUNE DISEASES
Authors: D. Desai, P. Khandwala, I. Tan
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The introduction of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment. ICIs augment antitumor activity by blocking the binding of checkpoint proteins with their partner proteins. This inhibition is a negative regulator on T cell cytotoxicity causing the unrestraint killing of tumor cells, a loss of self-tolerance, and increased risk of inducing autoimmunity.<sup>[[1]]</sup> <h3>Objectives</h3> The study was undertaken to establish correlation between the use of ICIs and autoimmune conditions (ACs), and to study trends in incidence and prevalence of ACs in patients treated with ICIs. <h3>Methods</h3> TrinetX, a global federated research network that provides a dataset of electronic medical records from different healthcare organizations (HCOs) was utilized. Initial query was made to isolate patients who had a diagnosis of "Neoplasm" (International Classification of Diseases, 10th version (ICD-10) Code C00 - D49). Two cohorts were made, on basis of ICIs use. Propensity score matching was carried out to match age, race and gender. Compare outcome analytic function was utilized to map the co-relation with ACs. ACs included were Systemic Connective Tissue Disorders (ICD-10:M30-M36), Rheumatoid Arthritis (ICD-10:M05, M06), Arthropathic Psoriasis (ICD10 L40.5). 9 FDA-approved checkpoint inhibitors were included in our study: Atezolizumab, Avelumab, Cemiplimab, Dostarlimab, Durvalumab, Ipilimumab, Nivolumab, Pembrolizumab, and Relatlimab.<sup>[2]</sup> <h3>Results</h3> A total of 12,009,334 patients had a diagnosis of neoplasm out of which 72,865 (0.61%) patients were taking ICIs. Patients in ICIs group were older as compared to patients in non-ICIs group (68 ±12.6 years vs 62.7±17.7 years). Males were predominant in ICIs group (58% vs 42%) while they were in minority in the non ICIs group (43% vs 57%). Caucasians were the predominant race followed by unknown race and then African Americans (76% vs 13% vs 9% in ICI group, and 63% vs 25% vs 10% in non-ICI group). 5.16% of patients in the ICIs group had ACs while only 4.17% of patients in non ICIs group had ACs (p&lt;0.0001). The hazard ratio (HR) of having ACs was higher in ICIs group as compared to non ICIs group (HR = 1.96, 95% confidence interval (CI), 1.898-2.024, p&lt;0.0001). After propensity score matching, both groups had 72,865 patients. 5.16% patients in the ICIs group had ACs, while only 4.46% of patients in the non ICIs group had ACs. HR was 1.925 (95% CI, 1.831-2.025, p&lt;0.0001). As shown in the graph below, the incidence of autoimmune conditions increased from 0.79% in 2015 to 2.16% in 2021 in ICIs group. Similarly, prevalence also increased from 2.97% in 2015 to 8.06% in 2021. <h3>Conclusion</h3> Although ICIs transformed the cancer management landscape, it is important to be aware of its effects on autoimmune disorders. Incidence and prevalence of ACs have increased in patients with neoplasm treated with ICI over the years. It can also be seen that HR of having outcome of ACs is higher in ICI group. There is a need for a prospective study to correlate the causality of development of AC with use of ICI. <h3>References</h3> [1]Tocut M., Brenner R., Zandman-Goddard G; Autoimmune phenomenon and disease in cancer patients treated with immune checkpoint inhibitors; Autoimmunity Reviews; June 2018; 17:6:610-616. [2]https://www.cancerresearch.org/treatment-types/immunomodulators <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.